Oriented External Electric Fields Regurating the Reaction Mechanism of CH4 Oxidation Catalyzed by Fe(IV)-Oxo-Corrolazine: Insight from Density Functional Calculations

Methane is the simplest alkane and can be used as an alternative energy source for oil and coal, but the greenhouse effect caused by its leakage into the air is not negligible, and its conversion into liquid methanol not only facilitates transportation, but also contributes to carbon neutrality. In order to find an efficient method for converting methane to methanol, CH4 oxidation catalyzed by Fe(IV)-Oxo-corrolazine (Fe(IV)-Oxo-Cz) and its reaction mechanism regulation by oriented external electric fields (OEEFs) are systematically studied by density functional calculations. The calculations show that Fe(IV)-Oxo-Cz can abstract one H atom from CH4 to form the intermediate with OH group connecting on the corrolazine ring, with the energy barrier of 25.44 kcal mol−1. And then the product methanol is formed through the following rebound reaction. Moreover, the energy barrier can be reduced to 20.72 kcal mol−1 through a two-state reaction pathway. Furthermore, the effect of OEEFs on the reaction is investigated. We found that OEEFs can effectively regulate the reaction by adjusting the stability of the reactant and the transition state through the interaction of electric field-molecular dipole moment. When the electric field is negative, the energy barrier of the reaction decreases with the increase of electric intensity. Moreover, the OEEF aligned along the intrinsic Fe‒O reaction axis can effectively regulate the ability of forming the OH on the corrolazine ring by adjusting the charges of O and H atoms. When the electric field intensity is −0.010 a.u., the OH can be directly rebounded to the CH3· before it is connecting on the corrolazine ring, thus forming the product directly from the transition state without passing through the intermediate with only an energy barrier of 17.34 kcal mol−1, which greatly improves the selectivity of the reaction.


INTRODUCTION
Compared with oil or coal, methane is an environment-friendly energy, but it is also a greenhouse gas, and its greenhouse effect is much larger than that of carbon dioxide (Chong et al., 2016;Denning et al., 2021;Huang et al., 2021;Sánchez-López et al., 2021). A quarter of the greenhouse effect caused by man-made greenhouse gases is caused by the leakage of methane into the atmosphere (Kemp et al., 2016). In 2021, the United Nations called for a reduction in methane emission in the atmosphere, aiming to reduce global methane emission by 30% by the end of the century (Brenneis et al., 2022). Therefore, if an efficient method can be found to convert methane into methanol efficiently and economically, it can not only solve the difficulty of methane transportation, but also provide a large number of cheap raw materials for industrial production and reduce methane pipelines leakage (Park et al., 2019;Yan et al., 2020;Januario et al., 2021), thus providing feasible methods for methane emission reduction.
Recently, Sason Shaik et al. (Hirao et al., 2008;Gorin et al., 2012;Fried and Boxer, 2015;Li et al., 2015;Akamatsu et al., 2017;Che et al., 2018;Ciampi et al., 2018;He et al., 2018;Yu and Coote, 2019;Shaik et al., 2020;Shaik et al., 2004b;Kraskov et al., 2021;Yu et al., 2021;Zhang et al., 2021;de Visser et al., 2022) found that oriented external electric fields (OEEFs) can be used as a new type of catalyst to catalyze reactions by stabilizing transition states through the interactions between OEEFs and the molecular dipole moments, and even can increase the selectivity of reactions through adjusting the direction of OEEFs. Through theoretical calculations, our group also found that the OEEFs can modulate the reaction process through the interactions with the dipole moment of the reaction molecules (Wang et al., 2019).
Herein, we systematically study the reaction process of the oxidation of methane to methanol catalyzed by Fe(IV)-Oxocorrolazine, and discuss the regulation of its reaction mechanism catalyzed by OEEFs, which provides a theoretical basis for the direct and efficient conversion of methane to methanol.

COMPUTATIONAL DETAILS
All the calculations were performed in Gaussian16 package (Frisch et al., 2016), using the B3LYP-D3(BJ) (Stephens et al., 1994;Grimme et al., 2010;Grimme et al., 2011) hybrid functional with the LANL2TZ (Roy et al., 2008) basis set coupled with the effective core potential for Fe atom and the all-electron 6-31++G (d,p) (Hariharan and Pople, 1973) basis set for other atoms. The structures of reactant (RC), transition state (TS), intermediate (INT) and product (P) were fully optimized without any symmetry constraints. Then the natures of these optimized structures were assessed by frequencies calculation, for RC, INT, and P with only real frequencies, and for TS with only one imaginary frequency. Moreover, all TS species were further verified by intrinsic reaction coordinate (IRC) calculations. The calculated output file was analyzed by Multiwfn to obtain the spin density (Lu and Chen, 2012).
As shown in Figure 1, using the keyword "Field = M ± N″, the two OEEFs, F z1 and F z2 along the Fe-O axis and O-H axis respectively, were applied to regulate the CH 4 oxidation reaction catalyzed by Fe(IV)-Oxo-Cz. The positive direction of the electric field vector follows the Gaussian 16 convention, i.e., the direction from negative charge to positive charge is F z > 0. The electric field intensity ranges from −0.010 a.u to +0.010 a.u. for F z1 and F z2 (1 a.u. = 51.4 V Å −1 ). The geometry structures of Fe(IV)-Oxo-Cz in doublet, quartet and sextet states were optimized and their relative energies and selective structure parameters are collected in Table 1. As seen from Table 1, the quartet state is lower in free energies than the double and sextet states by 10.25 and 40.05 kcal mol −1 , respectively (absolute energies in Supplementary Table S1). Moreover, the calculated Fe-O bond length in quartet state is 1.615 Å, which is close to the experimentally determined value of 1.640 Å (Cho et al., 2012). Therefore, the quartet state is the ground state, and due to the stronger interaction between the Fe atom and the O atom, the Fe atom deviates upward from the corrolazine ring, as shown in Figure 2. Furthermore, the spin densities and NPA charges for the different spin states of Fe(IV)-Oxo-Cz were calculated (see Supplementary Tables S2, S3). For the quartet state, the Fe-O moiety only occupied two single electrons, and the remaining one single electron was occupied by the corrolazine ring as shown in Figure 2. And the single electron occupying molecular orbitals (SOMO) of the quartet state Fe(IV)-Oxo-Cz is shown in Figure 3. Two single electrons are in the orthogonal π orbitals of the Fe-O moiety and the other mainly distributes on the corrolazine ring, which is exactly the same as the electronic configuration of Cpd-I (Huang and Groves, 2017;Zaragoza et al., 2017), reflecting the potential enzymatic catalytic activity of Fe(IV)-Oxo-Cz.

CH 4 Oxidation Catalyzed by Fe(IV)-Oxo-Corrolazine Under the Field-free Condition
Based on the quartet ground state structure of Fe(IV)-Oxo-Cz, the reaction between Fe(IV)-Oxo-Cz and CH 4 in quartet state in the absence of OEEF was studied. As illustrated in Figure 4; Then the product (P) CH 3 OH is produced through the rebound reaction where the newly formed OH is rapidly rebounded to the CH 3 · from Fe-corrolazine. (Cummins et al., 2020;Huang and Groves, 2017;Shaik et al., 2004a). And in this step, the reaction barrier is only 1.98 kcal mol −1 , and the reaction energy of 40.93 kcal mol −1 will promote the reaction to the right. Moreover, considering that the reaction may proceed at different potential energy surfaces, we further calculated the double state potential energy surface. As shown in Figure 4 and Supplementary Table S4, the TS1 of the double state is lower than that of the quartet state, indicating that the reaction is a twostate reaction and the reaction is easier to carry out (Schröder et al., 2000;Stuyver et al., 2020). However, considering that the quartet state of RC is the ground state, and the quartet state of P is much more stable than the double state, and that when the OEEF with F z1 = −0.010 a.u. is applied, the energy order of the quartet and double states of reactant dose not changed and there is no energy crossing points along the reaction pathway, so we further In order to explore the regulation mechanism of OEEFs in the reaction, we first systematically studied the effect of OEEFs on the TS1 of the reaction. As shown in Figure 5A, due to the application of OEEFs, the relative energies of the reaction TS1 change significantly. For F z > 0, the structure of TS1 is stabilized by OEEFs, and its relative energy decreases with the increase of the electric field intensity. While for F z < 0, OEEFs in different directions have different effects on the TS1. For F z1 , when it is in the range of 0~−0.002 a.u., the TS1 is destabilized by the OEEF, and its relative energy increases with the increase of the electric field intensity. However, as the electric field intensity further increases more than -0.002 a.u. the TS1 is stabilized by the OEEF again, and its relative energy decreases with the increase of the electric field intensity. For F z2 , the TS1 is always stabilized by the OEEF, and its relative energy decreases with the increase of the electric field intensity.
To explore the essential reason for the stability change of the TS1 effected by OEEFs, the dipole moments in z orientation of the TS1 of Fe(IV)-Oxo-Cz and CH 4 at different electric field intensities are analyzed. As shown in Figure 5B, for F z1 > 0, the dipole moment in z1 direction of the TS1 increases from -1.06 D in the electric field free to -8.58 D in F z1 = +0.010 a.u. Therefore, the TS1 is stabilized by the applied OEEFs originating from the attractive interaction between the increased dipole moment in z1 direction and the OEEF. When the OEEF is reversed to F z1 < 0, the interaction between the dipole moment and the OEEF becomes complex. For −0.002 a.u. < F z1 < 0, the OEEF decreases the dipole moment of in z1 direction of the TS1, and the repulsion between F z1 and the dipole moment of the TS1 destabilizes the TS1. However, when F z1 becomes more negative, it flips the orientation of the molecular dipole of the TS1. Therefore, the increasing OEEF increases the dipole moment in z1 orientation of the TS1, thus again stabilizing the TS1 originating from the attraction between the increased dipole moment and F z1 . For F z2 , the orientation of molecular dipole moment in z2 direction is opposite to the direction of the OEEF, and the dipole moment always increases with the increase of electric field intensity, thus always stabilizing the TS1 of the retion originating from the attractive interaction between the increased dipole moment in z2 direction and the OEEF.
Similar to the TS1, the RC of the reaction of Fe(IV)-Oxo-Cz and CH 4 are also effected by the OEEF remarkably. As shown in Figure 6, for F z1 and F z2 > 0, the dipole moment in z orientation   of the RC increases with the increase of OEEFs. Therefore, the RC is stabilized by OEEFs, originating from the attraction between OEEFs and the increased dipole moment in z orientation. For F z1 and F z2 < 0, the dipole moment in z orientation first decreases with the increase of the electric field intensity in the initial part of F z < 0, and then increases with the increase of the electric field intensity, which is more than -0.006 a.u. for F z1 and -0.002 a.u. for F z2 resulting from the reverse of the molecular dipole in z direction of the RC. Thus, the RC is first destabilized and then stabilized by OEEFs resulting from the repulsion and attraction between OEEFs and the increased dipole moment in z orientation, respectively.

The Effect of OEEFs on the Energy Barrier of CH 4 Oxidation Catalyzed by Fe(IV)-Oxo-Corrolazine
The effect of OEEFs on the energy barrier of the reaction of CH 4 oxidation by Fe(IV)-Oxo-Cz is further investigated. As shown in Table 3; Figure 7, for F z1 and F z2 > 0, the energy barriers of the reaction increase with the increase of electric field intensity, because the dipole moments in z direction of the RC and TS1 increase with the increase of electric field intensity, and the dipole moments of the RC is always larger than the TS1 in the electric intensity range, thus resulting in its stronger stabilization by OEEFs. However, for F z1 and F z2 < 0, the stabilization of the TS1 by OEEFs is always stronger FIGURE 5 | Plots of the relative energies (A) and the dipole moments (B) of the TS1 as a function of the applied OEEFs. The inset is the enlarged view at F z1 and F z2 = −0.005 a.u. to 0 a.u. black curve for F z1 and blue curve for F z2 . Frontiers in Chemistry | www.frontiersin.org June 2022 | Volume 10 | Article 896944 5 than that of the RC, originating from the stronger dipole moment of the TS1, so the energy barriers of the reaction decrease with the increase of electric field intensity, in which the energy barriers decrease to 17.34 and 21.16 kcal mol −1 for F z1 = −0.010 and F z2 = −0.010 a.u., respectively, thus greatly promoting the reaction. Especially for F z1 , it can more effectively regulate the reaction than F z2 , resulting from its greater slope of energy barrier curve in Figure 7. Moreover, as its direction is nearly perpendicular to the corrolazine ring, F z1 can be more easily aligned, thus making it easier to apply in practice.

OEEFs Optimizing the Process of CH 4 Oxidation Catalyzed by Fe(IV)-Oxo-Corrolazine
As shown in Table 4, for F z1 < 0, with the increase of electric field intensity, the negative charge of O atom and the positive charge of H atom in the TS1 decrease, while the O-H distance increases. Therefore, the ability of H to transfer to O to form stable the OH groups on the corrolazine ring decreases, which is the key process of forming the INT. When the intensity of the electric field reaches -0.010 a.u., both the negative charge of the O atom and the positive charge of the H atom reach the smallest, and the OH distance is the largest. Therefore, before the OH group forming on the corrolazine ring, it directly returns to the C atom through the rebound reaction from the P, as shown in Supplementary Figure S1, thereby simplifying the process of the reaction without passing through the INT to the product, thus avoiding the coupling between the intermediates to generate other products (Cho et al., 2012), greatly improving the selectivity of the reaction, and being beneficial to industrial applications.

CONCLUSION
Extensive density functional calculations have been carried out to explore the CH 4 oxidation reaction catalyzed by Fe(IV)-Oxo-Cz and its regulatory mechanism by OEEFs. The calculations show one H atom of CH 4 is captured by Fe(IV)-Oxo-Cz to form INT, in which OH group is connecting on the corrolazine ring, and then the product methanol is formed through the following rebound reaction. And the energy barrier of the reaction is 25.44 kcal mol −1 . Moreover, the energy barrier can be reduced to 20.72 kcal mol −1 through a two-state reaction pathway. To facilitate the reaction, we applied OEEFs F z1 and F z2 along the Fe-O axis and the O-H axis to modulate the reaction, respectively. When the positive OEEFs are applied, the energy barrier of the reaction increases with the increase of the electric field intensity. However, while flipping OEEFs to the negative direction, the energy barrier of the reaction decreases with the increase of the electric field intensity originating from the interaction of electric field-molecular dipole moment, which   can facilitate the reaction. Especially, the F z1 is easier be applied in practice because its direction is along the intrinsic Fe-O reaction axis approximately perpendicular to the corrolazine ring, and it can effectively modulate the ability of forming the OH on the corrolazine ring by adjusting the charge of O and H atoms. When its intensity is −0.010 a.u., F z1 can simplify the reaction path to directly form the reaction product from the transition state without passing through the intermediate, with only an energy barrier of 17.34 kcal mol −1 , in which the OH is directly rebounded to CH 3 · before it is connecting on the corrolazine ring, thus greatly improving the selectivity of the reaction.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

AUTHOR CONTRIBUTIONS
CZ, J-XL, and HW directed the research. JW conducted DFT calculations. JW and TL analyzed the data. All the authors discussed the results and co-write the manuscript.